Biosynthesis of 7-deazaguanosine-modified tRNA nucleosides: A new role for GTP cyclohydrolase I

Gabriella Phillips, Basma El Yacoubi, Benjamin Lyons, Sophie Alvarez, Dirk Iwata-Reuyl, Valérie De Crécy-Lagard

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Queuosine (Q) and archaeosine (G+) are hypermodified ribonucleosides found in tRNA. Q is present in the anticodon region of tRNA GUN in Eukarya and Bacteria, while G+ is found at position 15 in the D-loop of archaeal tRNA. Prokaryotes produce these 7-deazaguanosine derivatives de novo from GTP through the 7-cyano-7-deazaguanine (pre-Q 0) intermediate, but mammals import the free base, queuine, obtained from the diet or the intestinal flora. By combining the results of comparative genomic analysis with those of genetic studies, we show that the first enzyme of the folate pathway, GTP cyclohydrolase I (GCYH-I), encoded in Escherichia coli by folE, is also the first enzyme of pre-Q0 biosynthesis in both prokaryotic kingdoms. Indeed, tRNA extracted from an E. coli ΔfolE strain is devoid of Q and the deficiency is complemented by expressing GCYH-I-encoding genes from different bacterial or archaeal origins. In a similar fashion, tRNA extracted from a Haloferax volcanii strain carrying a deletion of the GCYH-I-encoding gene contains only traces of G+. These results link the production of a tRNA-modified base to primary metabolism and further clarify the biosynthetic pathway for these complex modified nucleosides.

Original languageEnglish (US)
Pages (from-to)7876-7884
Number of pages9
JournalJournal of bacteriology
Volume190
Issue number24
DOIs
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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